Neuroimaging predicts pathological subtypes of Alzheimer’s disease

Jenna Gregory, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP

Three pathological subtypes of Alzheimer’s disease (AD) are currently thought to exist, supported by distinct histological and clinical presentations. These are: typical AD, hippocampal-sparing AD and limbic-predominant AD [1]. The clinical presentations are accounted for by the loss of function of specific brain regions caused by generalised neurotoxicity. Intracellular neurofibrillary tangles comprised of Tau protein and extracellular plaques of pathological amyloid ß protein are found in the affected brain regions and these two proteinopathies are thought to cause neurotoxicity as their presence correlates well with the disease process. The resulting neurodegeneration presents as brain atrophy and is restricted to characteristic patterns in each of the three subtypes.

Using a case-controlled study the authors of a recent publication in the Lancet Neurology were therefore able to demonstrate the use of Magnetic Resonance Imaging (MRI) combined with volumetric analysis to highlight these specific areas of atrophy. Indeed this application of neuroimaging technique reliably predicted the pathological AD subtype seen at autopsy [2].

These results may be particularly beneficial for providing AD patients with accurate prognostic information as each of the subtypes is clinically distinct in presentation and disease-course, for example cognitive decline is more rapid with hipocampal-sparing subtype [1]. However, whilst the ability to distinguish between pathological subtypes of AD using imaging is reliable and consistent with autopsy results, it remains to be proven whether this will affect our clinical practice or future management. Nevertheless, these results do represent a step forwards in an area of extremely limited treatment options and poor diagnostic markers.


1. Murray ME, Graff-Radford NR, Ross OA, Petersen RC, Duara R, Dickson DW. Neuropathologically defined subtypes of Alzheimer’s disease with distinct clinical characteristics: a retrospective study. Lancet Neurol 2011; 10: 785–96. doi: 10.1016/S1474-4422(11)70156-9

2. Jennifer L Whitwell, Dennis W Dickson, Melissa E Murray, Stephen D Weigand, Nirubol Tosakulwong, Matthew L Senjem, David S Knopman, Bradley F Boeve, Joseph E Parisi, Ronald C Petersen, Cliff ord R Jack Jr, Keith A Josephs. Neuroimaging correlates of pathologically defi ned subtypes of Alzheimer’s disease: a case-control study. Lancet Neurol 2012; 11: 868–77. doi:10.1016/S1474-4422(12)70200-4

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